Tissue-characterization probe with effective sensor-to-tissue contact

ABSTRACT

The present invention relates to a device for tissue-characterization, designed for effective sensor-to-tissue contact. The device includes an element, having a rigid surface of a linear cross-section, on which at least one sensor is arranged, and a mechanism for applying a force to a soft tissue, the line of force being at an acute angle with the rigid surface, for stretching or stretching and pushing the soft tissue against the rigid surface, thus achieving effective contact between the tissue and the at least one sensor. In consequence, the accuracy of the sensing is improved. In accordance with another embodiment, a plurality of sensors is employed, arranged along a curved element, for providing three-dimensional information regarding the tissue, for example, by small-scale computerized tomography.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/350,102 filed on Feb. 9, 2006, which is a continuation-in-part (CIP)of pending U.S. patent application Ser. No. 11/196,732 filed on Aug. 4,2005.

The contents of all of the above applications are incorporated byreference as if fully set forth herein.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to local tissue characterization and moreparticularly, to a tissue-characterization probe with effectivesensor-to-tissue contact. The probe is further adapted for providingthree-dimensional information.

A large number of techniques and sensors are available today for tissuecharacterization, for example, to determine the presence of abnormaltissue, such as cancerous or pre-cancerous tissue. These may beincorporated into hand-held probes or miniature probes, adapted forinsertion into a body lumen or for use in minimally invasive surgery.While the operating principles of different tissue characterizationsensors differ, effective contact between the sensor and the tissue isoften essential for reliable results. For example, the presence of airbubbles between an ultrasound sensor and the tissue will interfere withultrasound measurements. Similarly, a liquid layer may interfere with anoptical spectroscopy sensor.

The use of suction, for engaging a medical instrument to a tissue, isknown. For example, U.S. Pat. No. 5,927,284, to Borst, entitled, “AMethod and Apparatus for Temporarily Immobilizing a Local Area ofTissue,” whose disclosure is incorporated herein by reference, describestemporarily immobilizing a local area of heart tissue to permit surgeryon a coronary vessel in that area without significant deterioration ofthe pumping function of the beating heart. The local area of hearttissue is immobilized to a degree sufficient to permit minimallyinvasive or micro-surgery on that area of the heart. A suction device isused to accomplish the immobilization. The suction device is coupled toa source of negative pressure. The suction device has a series ofsuction ports on one surface. Suction through the device causes suctionto be maintained at the ports. The device is shaped to conform to thesurface of the heart. Thus, when the device is placed on the surface ofthe heart and suction is created, the suction through the ports engagesthe surface of the heart. The suction device is further fixed orimmobilized to a stationary object, such as an operating table or asternal or rib retractor. Thus, the local area of the heart near thesuction device is temporarily fixed or immobilized relative to thestationary object while suction is maintained. In this fashion, thecoronary artery may be immobilized, even though the heart itself isstill beating so that a bypass graft may be performed. In addition, thesuction device may be used in either a conventional, open-chestenvironment or in a minimally-invasive, endoscopic environment.

Additionally, U.S. Pat. No. 6,728,565, to Wendlandt, entitled,“Diagnostic Catheter Using a Vacuum for Tissue Positioning,” whosedisclosure is incorporated herein by reference, describes the use of adiagnostic catheter, associated with a vacuum source, for attaching asensor to a tissue surface. The method includes inserting a catheterwith a sensor at its distal end into the body of a patient, applyingsuction through the catheter, to draw tissue into a predeterminedsensing position for the sensor, and analyzing the tissue with thesensor. The degree of vacuum may be adjusted, so that only the requiredamount of force is used to maintain contact between the sensor orsensors and the tissue being analyzed.

U.S. Pat. No. 6,090,041, to Clark, entitled, “Vacuum Actuated SurgicalRetractor and Methods,” whose disclosure is incorporated herein byreference, describes a surgical retractor for retracting body tissue ororgans, using suction. The surgical retractor includes an end pieceadapted for sealing engagement with body tissue, the end piece having atleast one suction port therein, the at least one suction port operablylinked to at least one vacuum line. Suction supplied to the at least onesuction port may be controlled by a vacuum control unit. Retractors ofthe invention may be provided in a range of shapes and sizes, accordingto the intended application or tissue to be retracted. A method formaking a vacuum actuated retractor of the invention is disclosed,together with a method for automatically retracting body tissue.

U.S. Pat. No. 6,500,112, to Khouri, entitled, “Vacuum Dome withSupporting Rim and Rim Cushion,” whose disclosure is incorporated hereinby reference, describes the use of vacuum for tissue stretching, toenlarge a soft tissue, for example after a breast surgery, or to correcta deformity. It utilizes a generally rigid dome, capable of withstandinga pressure differential, with a rim cushion underlying the rim of thedome, for supporting the rim against the patient's skin surface. The rimmay be generally wider than the dome in order to distribute theattendant forces across a greater surface and avoid tissue damage. Asticky sole underlies the rim cushion and seals the rim cushion to thepatient's skin, to thereby preserve the vacuum within the dome. Thesticky sole may be any adhesive material or may be achieved through theuse of an appropriate material for the rim cushion itself. Unlike theother references, described hereinabove, in U.S. Pat. No. 6,500,112, thevacuum is used for its therapeutic effect, i.e., tissue stretching, toenlarge a soft tissue or to correct a deformity, rather than as meansfor attaching another instrument.

While the aforementioned devices relate to engagement with a tissue,they do not address the quality of the engagement surface. There is thusa need for devices and methods for ensuring effective contact between atissue-characterization sensor and a tissue, free of air, liquid andforeign matter.

SUMMARY OF THE INVENTION

The present relates to a device for tissue-characterization, designedfor effective sensor-to-tissue contact. The device includes an element,having a rigid surface of a linear cross-section, on which at least onesensor is arranged, and a mechanism for applying a force to a softtissue, the line of force being at an acute angle with the rigidsurface, for stretching or stretching and pushing the soft tissueagainst the rigid surface, thus achieving effective contact between thetissue and the at least one sensor. In consequence, the accuracy of thesensing is improved. In accordance with another embodiment, a pluralityof sensors is employed, arranged along a curved element, for providingthree-dimensional information regarding the tissue, for example, bysmall-scale computerized tomography.

There is thus provided, in accordance with an aspect of the presentinvention, a device, comprising:

an element, which defines a rigid surface of a linear cross-section,configured to make contact with a tissue;

at least one sensor, in physical contact with the rigid surface; and

a mechanism, adapted for applying a force to the tissue, the line offorce being at an acute angle with the rigid surface, for stretching thetissue against the rigid surface, thus achieving effective contactbetween the tissue and the rigid surface.

Additionally, the stretching further includes stretching and pushing.

Furthermore, the acute angle is between 30 degrees and 60 degrees.

Additionally, the effective contact is a contact level of at least 95%.

Furthermore, the effective contact is a contact level of at least 99%.

Additionally, the effective contact is a contact level of at least99.5%.

Furthermore, the effective contact is a contact level of at least 99.8%.

Additionally, the sensor is an irradiative sensor of a wavelength λ, andan average distance t1, between external-most surfaces of the tissue andthe sensor, is such that t1<λ/3.

Furthermore, the sensor is an irradiative sensor of a wavelength λ, andan average distance t1 between external-most surfaces of the tissue andthe sensor is such that t1<λ/10.

Additionally, the sensor is an irradiative sensor of a wavelength λ, andan average distance t1, between external-most surfaces of the tissue andthe sensor is such that t1<λ/100.

Alternatively, an average distance t1, between external-most surfaces ofthe tissue and the sensor, is less than 500 Angstroms.

Additionally, an average distance t1, between external-most surfaces ofthe tissue and the sensor, is less than 50 Angstroms.

Furthermore, an average distance t1, between external-most surfaces ofthe tissue and the sensor, is less than 5 Angstroms.

Additionally, the at least one sensor is an irradiative sensor, selectedfrom the group consisting of an optical sensor, an X-ray sensor, an RFsensor, a MW sensor, an infrared thermography sensor, and an ultrasoundsensor.

Furthermore, the at least one sensor is selected from the groupconsisting of an MR sensor, an impedance sensor, a temperature sensor, abiosensor, a chemical sensor, a radioactive-emission sensor, anonirradiative RF sensor, and a mechanical sensor.

Additionally, the device further comprises a plurality of sensors.

Alternatively, the at least one sensor includes at least two differenttypes of sensors.

Additionally, the at least one sensor includes at least two differenttypes of sensors, selected from the group consisting of optical sensors,X-ray sensors, RF sensors, MW sensors, infrared thermography sensors,ultrasound sensors, MR sensors, impedance sensors, temperature sensors,biosensors, chemical sensors, radioactive-emission sensors, mechanicalsensors, and nonirradiative RF sensors.

Furthermore, the element defines a curvature for obtainingthree-dimensional information, and further wherein the plurality ofsensors includes at least two sensors, arranged along the curvature,each defining a viewing angle, the at least two sensors sharing aportion of their viewing angles so as to obtain three-dimensionalinformation.

Additionally, the plurality of sensors includes at least four sensors,arranged as at least two pairs of sensors, each pair being ofsubstantially identical sensors, and each pair representing a differenttype of sensor, for providing three-dimensional information by at leasttwo modalities.

Furthermore, the three-dimensional information includes small-scalecomputerized tomography.

Additionally, the mechanism is suction.

Alternatively, the mechanism is tweezers-like.

Alternatively, the mechanism exerts physical pressure on the tissue.

There is thus also provided, in accordance with another aspect of thepresent invention, a tissue-characterization probe, comprising:

a housing, which defines proximal and distal ends, with respect to atissue;

an element, at the proximal end of the probe, the element defining arigid surface of a linear cross-section, configured to make contact withthe tissue;

a mechanism, adapted for applying a force to the tissue, the line offorce being at an acute angle with the rigid surface, for stretching thetissue against the rigid surface, thus achieving effective contactbetween the tissue and the rigid surface;

at least one sensor, in physical contact with the rigid surface; and

at least one signal communication line, for providing communicationbetween a signal analyzer and the at least one sensor.

Additionally, the mechanism is suction.

Furthermore, a pump, which provides the suction, is arranged within thehousing.

Additionally, the suction is provided by a channel, arranged within thehousing and in communication with an external vacuum source.

Furthermore, the channel is operative to drain off tissue fluids.

Additionally, the probe is configured for an application, selected fromthe group consisting of extracorporeal application to a skin,intracorporeal insertion through a body lumen, intracorporeal insertionfor a minimally invasive procedure, and application to subcutaneoustissue, during open surgery.

There is thus provided, in accordance with yet another aspect of thepresent invention, a tissue-characterization system, comprising:

a housing, which defines proximal and distal ends, with respect to atissue;

an element, at the proximal end of the probe, the element defining arigid surface of a linear cross-section, configured to make contact witha tissue;

a mechanism, adapted for applying a force to the tissue, the line offorce being at an acute angle with the rigid surface, for stretching thetissue against the rigid surface, thus achieving effective contactbetween the tissue and the rigid surface;

at least one sensor, in physical contact with the rigid surface;

a signal analyzer; and

at least one signal communication line, for providing communicationbetween the signal analyzer and the at least one sensor.

There is thus provided, in accordance with still another aspect of thepresent invention, a method of tissue characterization, comprising:

providing a tissue characterization probe, which comprises:

-   -   an element, which defines a rigid surface of a linear        cross-section, configured to make contact with a tissue;    -   at least one sensor, in physical contact with the rigid surface;        and

a mechanism, adapted for applying a force to the tissue, the line offorce being at an acute angle with the rigid surface, for stretching thetissue against the rigid surface, thus achieving effective contactbetween the tissue and the rigid surface;

applying a force to the tissue, the line of force being at an acuteangle with the rigid surface, for stretching the tissue against therigid surface, thus achieving effective contact between the tissue andthe rigid surface; and

characterizing the tissue with the at least one sensor.

There is thus provided, in accordance with yet another aspect of thepresent invention, a device, comprising:

an element, which defines a surface with a curvature in a firstdirection, the curvature being at least greater than that of a circlehaving a diameter of 8 cm; and

at least two sensors, arranged along the curvature, each defining aviewing angle into a volume, the at least two sensors sharing a portionof their viewing angles so as to obtain three-dimensional information ofthe volume.

Additionally, the curvature is greater than that of a circle having adiameter of about 6 cm.

Furthermore, the curvature is greater than that of a circle having adiameter of about 4 cm.

Additionally, the curvature is greater than that of a circle having adiameter of about 2 cm.

Furthermore, the curvature is greater than that of a circle having adiameter of about 1 cm.

Additionally, the curvature is greater than that of a circle having adiameter of about 0.8 cm.

Additionally, the at least two sensors include at least four sensors,arranged as at least two pairs of sensors, each pair being ofsubstantially identical sensors arranged along the curvature, and eachpair representing a different type of sensors, for providingthree-dimensional information by at least two modalities.

There is thus provided, in accordance with still another aspect of thepresent invention, a tissue-characterization probe, comprising:

a housing, which defines proximal and distal ends, with respect to atissue,

an element, which defines a surface with a curvature in a firstdirection, the curvature being at least greater than that of a circlehaving a diameter of 8 cm;

at least two sensors, arranged along the curvature, each defining aviewing angle into a volume, the at least two sensors sharing a portionof their viewing angles so as to obtain three-dimensional information ofthe volume; and

a signal communication architecture, for providing communication betweena signal analyzer and the at least two sensors.

Additionally, the probe is configured for insertion to a body lumen.

Alternatively, the probe is configured for insertion for insertionintracorporeally, for minimally invasive procedures.

Alternatively, the probe is configured for insertion for insertionintracorporeally, during open surgery.

Alternatively, the probe is configured for extracorporeal application,wherein the tissue is a skin.

There is thus provided, in accordance with still another aspect of thepresent invention, a tissue-characterization system, comprising:

a housing, which defines proximal and distal ends, with respect to atissue,

an element, which defines a surface with a curvature in a firstdirection, the curvature being at least greater than that of a circlehaving a diameter of 8 cm; and

at least two sensors, arranged along the curvature, each defining aviewing angle into a volume, the at least two sensors sharing a portionof their viewing angles so as to obtain three-dimensional information ofthe volume;

a signal analyzer; and

a signal communication architecture, for providing communication betweena signal analyzer and one of the at least two sensors.

There is thus provided, in accordance with yet another aspect of thepresent invention, a method of tissue characterization, for obtainingthree-dimensional information of a volumetric region within the tissue,comprising:

providing an element, which defines a surface with a curvature in afirst direction, having a diameter which is less than 8 cm; and

arranging at least two sensors on the curvature, each defining a viewingangle into a volumetric region, the at least two sensors sharing aportion of their viewing angles;

performing measurements with the at least two sensors; and

analyzing the measurements to obtain the three-dimensional informationof the volume.

There is thus provided, in accordance with still another aspect of thepresent invention, a method of tissue characterization, comprising:

providing an element, which defines a surface with a curvature in afirst direction, the curvature having a diameter which is less than 8cm;

arranging at least two pairs of sensors along the curvature, each pairbeing of substantially identical sensors, and each pair representing adifferent type of sensors, for providing three-dimensional informationby at least two modalities;

performing measurements with the at least two pairs of sensors; and

analyzing the measurements to obtain the three-dimensional informationof a volume, by the at least two modalities.

There is thus provided, in accordance with yet another aspect of thepresent invention, a device for tissue characterization, comprising:

a structure, formed of a rigid surface configured as a truncated cone,having a first cross-sectional configuration defining a diameter andhaving a second cross-sectional configuration defining an axis;

a first mechanism, associated with the structure, configured for causinga force to be exerted on a tissue, in a direction, along the axis, at anacute angle α to the rigid surface, for fixing the tissue to thestructure, so as to substantially immobilize the tissue; and

a second mechanism, associated with the structure, configured forpressing at least one piston sensor against an external surface of theimmobilized tissue, thereby exerting a counter force on the immobilizedtissue,

wherein at least a component of the force is in opposition to at least acomponent of the counter force, forcing the immobilized tissue againstthe at least one piston sensor, and forcing the at least one pistonsensor against the immobilized tissue, bringing about an effectivecontact between the at least one piston sensor and the immobilizedtissue.

Additionally, the at least one piston sensor includes at least twopiston sensors of a same type.

Furthermore, the at least one piston sensor includes at least two pistonsensors of different types.

Additionally, the probe includes at least one cone sensor, arranged onthe rigid surface.

Furthermore, the probe includes at least two cone sensors, arranged onthe rigid surface of the linear cross section.

Additionally, wherein the at least two cone sensors are arranged alongthe curvature, each cone sensor defining a viewing angle, the at leasttwo cone sensors sharing a portion of their viewing angles so as toobtain three-dimensional information.

Furthermore, the at least one cone sensor includes at least four conesensors, arranged as at least two pairs of cone sensors, each pair beingof substantially identical cone sensors, and each pair representing adifferent type of cone sensor, for providing three-dimensionalinformation by at least two modalities.

Additionally, wherein the first mechanism is a suction source, forfixing and substantially immobilizing the tissue, by suction.

There is thus provided, in accordance with still another aspect of thepresent invention, a tissue characterization probe, comprising:

a housing;

a structure, formed of a rigid surface of a conical cross-section,having a diameter in a first direction and an axis in a seconddirection, and a rigid surface;

a first mechanism, associated with the structure, configured forexerting a force on a tissue, in the second direction, along the axis,at an acute angle α to the rigid surface, for fixing the tissue to thestructure, so as to substantially immobilize the tissue; and

a second mechanism, associated with the structure, configured forpressing at least one piston sensor against an external surface of theimmobilized tissue, thereby exerting a counter force on the immobilizedtissue,

wherein at least a component of the force is in opposition to at least acomponent of the counter force, forcing the immobilized tissue againstthe at least one piston sensor, and forcing the piston sensor againstthe immobilized tissue, bringing about an effective contact between theat least one piston sensor and the immobilized tissue; and

a signal communication architecture, for providing communication betweena signal analyzer and the at least one piston sensor.

Additionally, the probe is configured for an application, selected fromthe group consisting of extracorporeal application to a skin,intracorporeal insertion through a body lumen, intracorporeal insertionfor a minimally invasive procedure, and application to subcutaneoustissue, during open surgery.

There is thus provided, in accordance with still another aspect of thepresent invention, a system for tissue characterization, comprising:

a housing;

a structure, formed of a rigid surface of a conical cross-section,having a diameter in a first direction and an axis in a seconddirection, and a rigid surface;

a first mechanism, associated with the structure, configured forexerting a force on a tissue, in the second direction, along the axis,at an acute angle α to the rigid surface, for fixing the tissue to thestructure, so as to substantially immobilize the tissue; and

a second mechanism, associated with the structure, configured forpressing at least one piston sensor against an external surface of theimmobilized tissue, thereby exerting a counter force on the immobilizedtissue,

wherein at least a component of the force is in opposition to at least acomponent of the counter force, forcing the immobilized tissue againstthe at least one piston sensor, and forcing the piston sensor againstthe immobilized tissue, bringing about an effective contact between theat least one piston sensor and the immobilized tissue;

a signal analyzer; and

a signal communication architecture, for providing communication betweenthe signal analyzer and the at least one piston sensor.

There is thus provided, in accordance with yet another aspect of thepresent invention, a method for tissue characterization, comprising:

providing a device for tissue characterization, which comprises:

a structure, formed of a rigid surface of a conical cross-section,having a diameter in a first direction and an axis in a seconddirection, and a rigid surface;

a first mechanism, associated with the structure, configured forapplying a force to on a tissue, in a second direction along the axis,at an acute angle α to the rigid surface, for fixing the tissue to thestructure, so as to substantially immobilize the tissue; and

a second mechanism, associated with the structure, configured forpressing at least one piston sensor against an external surface of theimmobilized tissue, thereby exerting a counter force on the immobilizedtissue,

wherein at least a component of the force is in opposition to at least acomponent of the counter force, forcing the immobilized tissue againstthe at least one piston sensor, and forcing the at least one pistonsensor against the immobilized tissue, bringing about an effectivecontact between the at least one piston sensor and the immobilizedtissue;

fixing the tissue to the structure, thus substantially immobilizing thetissue; and

pressing the at least one piston sensor against the external surface ofthe immobilized tissue, thereby exerting the counter force on theimmobilized tissue, wherein at least the component of the force is inopposition to at least the component of the counter force, forcing theimmobilized tissue against the at least one piston sensor, and forcingthe at least one piston sensor against the immobilized tissue, thusbringing about the effective contact between the at least one pistonsensor and the immobilized tissue; and

characterizing the tissue with the at least one piston sensor.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the patentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and are notintended to be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIGS. 1A-1G, and 1N schematically illustrate a longitudinalcross-section of a device, for effective sensor-to-tissue contact, inaccordance with some embodiments of the present invention;

FIGS. 1H-1L schematically illustrate situations of potentially poorcontact between a tissue and a device, as seen in a longitudinalcross-section, in accordance with the understanding the presentinvention;

FIG. 1M schematically illustrates an effective contact between a tissueand a device, as seen in a longitudinal cross-section, in accordancewith the embodiments of the present invention;

FIGS. 1O-1V schematically illustrate various transverse and longitudinalcross sections of a device, in accordance with some embodiments of thepresent invention.

FIGS. 2A-2E schematically illustrate, in longitudinal cross-sectionalview, a probe for tissue characterization, constructed with the deviceof the present invention;

FIG. 3 schematically illustrates a system for tissue characterization,in accordance with some embodiments of the present invention;

FIGS. 4A and 4B schematically illustrate a first arrangement of thesensors in the device, constructed in accordance with some embodimentsof the present invention;

FIG. 5 is a flowchart illustrating a method of tissue characterization,by improving a contact level between a tissue and a sensor, inaccordance with some embodiments of the present invention;

FIGS. 6A-6N schematically illustrate arrangements of the sensors in thedevice, for providing three-dimensional information, in accordance withfurther embodiments of the present invention;

FIG. 6O is a flowchart illustrating a method of tissue characterizationin three-dimensions, with small-scale computerized tomography, inaccordance with some embodiments of the present invention;

FIGS. 7A-7C schematically illustrate another configuration for effectivecontact, in accordance with an embodiment of the present invention;

FIGS. 7D-7F schematically illustrate another configuration for effectivecontact, in accordance with another embodiment of the present invention;

FIGS. 7G-7H schematically illustrate configurations with several typesof sensors, in accordance with embodiments of the present invention;

FIG. 8 schematically illustrates a first sensor construction, inaccordance with some embodiments of the present invention;

FIG. 9 schematically illustrates a second sensor construction fortransmission sensing, in accordance with some embodiments of the presentinvention; and

FIGS. 10A and 10B schematically illustrate optical sensor constructions,in accordance with some embodiments of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to a device for tissue-characterization,designed for effective sensor-to-tissue contact. The device includes anelement, having a rigid surface of a linear cross-section, on which atleast one sensor is arranged, and a mechanism for applying a force to asoft tissue, the line of force being at an acute angle with the rigidsurface, for stretching or stretching and pushing the soft tissueagainst the rigid surface, thus achieving effective contact between thetissue and the at least one sensor. In consequence, the accuracy of thesensing is improved. In accordance with another embodiment, a pluralityof sensors is employed, arranged along a curved element, for providingthree-dimensional information regarding the tissue, for example, bysmall-scale computerized tomography.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

The principles and operation of the device for tissue-characterization,according to some embodiments of the present invention, may be betterunderstood with reference to the drawings and accompanying descriptions.

Referring now to the drawings, FIGS. 1A-1G and 1N schematicallyillustrate a longitudinal cross-section of a device 10, for effectivesensor-to-tissue contact, in accordance with some embodiments of thepresent invention.

Accordingly, the device 10 includes an element 20, configured to makecontact with a tissue 44, which is at a proximal end 29. As seen inFIGS. 1A-1E, and 1N the element 20 may be shaped as a cone, having abase 26. However, as seen in FIG. 1F, other shapes may similarly beused. Some of these are described hereinbelow, in conjunction with FIGS.1O-1V.

The tissue 44 is a soft tissue, such as the tissue of muscle, skin, fat,internal organs, internal interfaces and the like, which generallyyields under pressure.

Preferably, the element 20 includes a section of a length L, having alinear cross section, and forming a rigid surface 22. The contact withthe tissue 44 is made along the rigid surface 22 of the preferablylinear cross section.

Additionally, the device 10 includes at least one sensor 24, associatedwith the rigid surface 22. A plurality of sensors 24 may be employed.The at least one sensor 24 may be embedded within or mounted on therigid surface 22.

Furthermore, the device 10 includes a mechanism 19, adapted for applyinga force F to the tissue 44, the line of force being at an acute angle αto the rigid surface 22, for stretching or stretching and pushing thetissue 44 against the rigid surface 22, thus achieving effective contactbetween the tissue 44 and the rigid surface 22. In consequence,effective contact between the tissue 44 and the at least one sensor 24is formed, and the accuracy of the sensing is improved.

FIG. 1B illustrates the angular relation between the force F and therigid surface 22. Intuitively, one may observe that were the force Fparallel with or perpendicular to the rigid surface 22, the desiredstretching of the tissue 44 against the rigid surface 22 would nothappen. The acute angle α between the line of force F and the rigidsurface 22 is essential for the practice of the present invention.Preferably, the acute angle α is between about 30 degrees and about 60degrees, yet other values of acute angles may also be used.

Additionally, one may observe that were the surface 22 curved, thestretching of the tissue 44 against the rigid surface 22 would not beuniform along the section of length L. Thus in accordance with thepreferred embodiment of the present invention, the surface 22 has alinear cross section.

As seen in FIG. 1C, the mechanism 19, which provides the force F, may bea vacuum source 32, for essentially sucking the tissue 44 into theelement 20.

FIG. 1N illustrates a similar situation, but with a single sensor 24, inaccordance with some embodiments of the present invention.

Alternatively, as seen in FIG. 1D, the mechanism 19 may be a mechanicaltool, for example, a tweezers-like tool 13, for pulling the tissue 44into the element 20.

Alternatively still, as seen in FIGS. 1E and 1F, the mechanism 19 may beanother mechanical tool, for example, a mallet-like tool 17, forpressing the tissue 44 into the element 20.

FIG. 1G schematically illustrates still another example of the mechanism19, for applying the force F to the tissue 44, at the acute angle α tothe rigid surface 22, wherein the rigid surface 22 may be a flat plate.The mechanism 19 may be, for example, a piston-cylinder configuration,arranged at the angle α to the flat plate, operative as the element 20,and having the rigid surface 22, in which the sensors 24 are embedded.

Referring further to the drawings, FIGS. 1H-1L schematically illustratesituations of potentially poor contact between the tissue 44 and therigid surface 22 of the element 20, in which the sensors 24 areembedded, as seen in a longitudinal cross-section of the device 10, inaccordance with the understanding of the present invention. In contrast,FIG. 1M schematically illustrates an effective contact between thetissue and the device 10, as seen in the longitudinal cross-section, inaccordance with embodiments of the present invention.

FIG. 1H is a cross-sectional view of an interface 45, between the rigidsurface 22 of the element 20 and the at least one sensor 24, on the onehand, and the tissue 44, on the other. A section 43 is marked andenlarged in FIGS. 1I-1M, hereinbelow.

FIG. 1I provides a cross-sectional view of the interface 45, at thesection 43, showing bubbles 46 of air or fluids, and (or) inclusions 47of foreign matter, which reduce and otherwise deteriorate the contactarea between the tissue 44 and the at least one sensor 24, along theinterface 45.

FIG. 1J also provides the cross-sectional view of the interface 45, atthe section 43, showing that tissue folds 48, possibly with bubbles 46and (or) inclusions 47, may also reduce and otherwise deteriorate thecontact area between the tissue 44 and the at least one sensor 24, alongthe interface 45.

FIG. 1K provides a view of the interface 45, at the section 43, from thedirection of an arrow 11 of FIG. 1H, showing the bubbles 46 and theinclusions 47, deteriorating the contact at the interface 45.

Defining:

-   -   Actual contact area A(actual), as the actual contact area        between the rigid surface 22 and the tissue 44;    -   Overall contact area A(interface), as the whole area of the        interface 45; and    -   Bubble and inclusions area A(bubbles and inclusions), as an area        covered by bubbles 46 of air and (or) fluid, and (or) by        inclusions 47 of foreign matter,        one may calculate the actual contact area and a contact level,        as follows:

$\begin{matrix}{{{A({actual})} = {{A({interface})} - {A\left( {{bubbles}\mspace{14mu}{and}\mspace{14mu}{inclusions}} \right)}}},{and},} & \lbrack 1\rbrack \\{{{Contact}\mspace{14mu}{Level}} = {\frac{A({actual})}{A({interface})}.}} & \lbrack 2\rbrack\end{matrix}$

Furthermore, one can quantify the effect of the bubbles 46 and theinclusions 47, and evaluate if the interface 45 is acceptable for tissuecharacterization, with a given sensor.

Embodiments of the present invention are aimed at achieving effectivecontact, which is a contact level of at least 95%. Preferably, thecontact level is greater than 98%. More preferably, the contact level isat least 99.5%, and even at least 99.8%.

FIG. 1L provides the cross-sectional view of the interface 45, at thesection 43, with reference to the at least one irradiative sensor 24,showing a situation where the edge surface of the irradiative sensor 24and the external-most surface of the tissue 44 are slightly apart, by anaverage distance t, so that in effect, there are three interfaces 45A,45B, and 45C, which may operate as three distinct reflective surfaces toincoming radiation 52. The first, the surface 45A, is the edge surfaceof the at least one sensor 24 (which is essentially the same as therigid surface 22), the second, the surface 45B, is the external-mostsurface of the tissue 44, and the third, the surface 45C, is a jointinterface of the edge surface of the at least one sensor 24 and theexternal-most surface of the tissue 44, when there is substantiallycomplete contact. This effect may be important for radiation of awavelength λ, for which the average distance t and the radiationwavelength λ are of a same order of magnitude, and in consequence, threereflections 54A, 54B, and 54C may be observed, from the interfaces 45A,45B, 45C, respectively, rather than the single reflection 54C, of thejoint interface.

In contrast with FIGS. 1H-1L, FIG. 1M schematically illustrateseffective sensor-to-tissue contact, as a consequence of the balance offorce diagram of FIG. 1G, in accordance with some embodiments of thepresent invention.

Accordingly, the interface 45 is substantially free of bubbles 46,foreign inclusions 47, and tissue folds 48, leading to effectivecontact, between the tissue 44 and the at least one sensor 24, theeffective contact being defined as a contact level of at least 95%,preferably, at least 98%, and more preferably, at least 99.5% and evenat least 99.8%.

Additionally, in accordance with embodiments of the present invention,which relate to sensors, operating with a wavelength λ, the effectivecontact may be further defined as a contact, for which the relationshipbetween the wavelength λ and an average distance t1, the averagedistance after achieving effective contact, (see FIG. 1M) is such thatt1<λ/3, and preferably, t1<λ/10, and more preferably, t1<λ/100.

Additionally or alternatively, the effective contact may be defined inabsolute terms. Accordingly, the average distance t1 is less than 500Angstroms, preferably the average distance t1 is less than 50 Angstroms,and more preferably, the average distance t1 is less than 5 Angstroms.

Referring further to the drawings, FIGS. 1O-1V schematically illustratevarious transverse and longitudinal cross sections of the element 20, inaccordance with some embodiments of the present invention. All areassociated with the rigid surface 22 of the linear cross section,arranged at the angle α to the line of force F.

Accordingly, the transverse cross sections may be a circle (FIG. 1O), anellipse (FIG. 1P), an arc (FIG. 1Q), or a line, associated with a flatplate (FIG. 1R), while the longitudinal cross sections may be atrapezoid (FIG. 1S), a triangle (FIG. 1T), a section of a trapezoid ortriangle (FIG. 1U), or a line (FIG. 1V).

Thus, the overall shape of the element 20 may be a cone, with a circularor an elliptical cross section, with a base, or with no base, a sectionof a cone, or a flat plate.

Referring further to the drawings, FIGS. 2A-2E schematically illustratea probe 50 for tissue characterization, constructed with the device 10of the present invention. The probe 50 includes a housing 12, whichincludes the device 10 with the element 20 having a conical shape, asdescribed hereinabove, in conjunction with FIGS. 1A-1V, and the at leastone sensor 24. In accordance with an embodiment of the presentinvention, the probe 50 is hand-held, and may include a handle 14, foreasy carrying. It will be appreciated that the probe 50 may also beemployed for minimally invasive surgery, for example, for insertion viaa trocar valve, or as an intracorporeal probe, adapted for insertion viaa body lumen. The probe 50 may also be employed in open surgery, or forcharacterizing external skin.

As seen in FIG. 2A, in a longitudinal cross-sectional view, at least onesignal communication line 16 leads from the at least one sensor 24 to aconnector 36, preferably, at a distal end 21, associated with a cable38, which provides power and signal communication with asignal-generation and analyzing station 70 described hereinbelow inconjunction with FIG. 3. A plurality of sensors 24 and a plurality ofsignal communication lines 16 may be employed. The at least one signalcommunication line may be a transmission line, for example, a coaxialcable, or an optical fiber.

As seen in FIG. 2B, in the longitudinal cross-sectional view, a battery80 and a transceiver 82 may be employed, for example, located at thedistal end 21, for wireless operation of the probe 50 and for wirelesscommunication with the signal-generation and analyzer station 60. Itwill be appreciated that the battery 80 may be rechargeable.

The probe 50 may further include a pump 30, receiving power via a powerline 37 and in fluid communication with the element 20, for providingsuction to the cone 20, via a channel 32, leading to an orifice 34 inthe element 20.

As seen in FIG. 2C, in the longitudinal cross-sectional view, the probe50 may be used for characterizing the soft tissue 44, for example, of abreast 42 of a body 40, during open surgery. When suction is applied tothe soft tissue 44, it is drawn into the element 20, maintainingeffective contact with the at least one sensor 24.

Additionally, during surgery, fluids 46 may be drawn as well anddirected by a channel 33 to a fluid trap 35, which may be emptied via avalve 31.

As seen in FIG. 2D, in the longitudinal cross-sectional view, a vacuumsource (not shown) external to the probe 50 may be used, via a vacuumline 39. A sealing flap 28, along the vacuum line 39, may close whenvacuum is applied, creating suction in the element 20. The vacuum line39 may connect with a pump 30 and the fluid trap 35. Alternatively, thevacuum line 39 and the pump 30 may be external to the probe 50, asdescribed hereinbelow, in conjunction with FIG. 3.

As seen in FIGS. 2A-2D, the probe 50 may further include at least onecontrol switch 18, for initiating the measurement by the at least onesensor 24, or the plurality of sensors 24, and for controlling the pump30 (FIGS. 2A-2C). Additionally, two control switches, 18A and 18B may beprovided, one for operating the sensor or sensors 24 and the other foroperating the pump 30. A junction 15 may be provided as a switchingstation, communicating with the at least one control switch 18, thesignal communication lines 16, and the pump power line 37. It will beappreciated that the at least one sensor 24 or the plurality of sensors24 may have a “standby” setting, and be set on standby, prior tooperation.

FIG. 2E provides a perspective view of the probe 50, according to someembodiments of the present invention.

Referring further to the drawings, FIG. 3 schematically illustrates asystem 70 for tissue characterization, in accordance with someembodiments of the present invention. Preferably, the system 70 includesthe probe 50, having the device 10 with the element 20 and at least onesensor 24, designed in accordance with some embodiments of the presentinvention. The probe 50 may be in fluid communication with an externalfluid trap 35 and an external pump 30. Alternatively, these may be builtinto the probe 50.

Preferably, a signal generator and analyzer 60 communicates with thesensors 24, either via a cable 38 or in a wireless manner, as known. Thesignal generator and analyzer 60 may include a built-in computer, or maycommunicate with a computer station 72, which analyzes measurementsperformed by the probe 50. Alternatively, a miniaturized signalgenerator and analyzer 60 and possibly also a microcomputer (not shown)may be built into the probe 50. It will be appreciated that separateunits may be employed for the signal generator and the signal analyzer.Additionally, some sensors are passive and do not require signalgenerators. For example, a temperature sensor, or a radioactive-emissionsensor do not require signal generators.

Referring further to the drawings, FIGS. 4A and 4B schematicallyillustrate a first arrangement of the at least one sensor 24 in thedevice 10, in accordance with some embodiments of the present invention.The element 20 may be shaped as a cone or as another shape having therigid surface 22 of linear cross section, arranged at an acute angle tothe applied force, and the at least one sensor 24 or the plurality ofthe sensors 24 may be embedded within or mounted on the rigid surface 22of the element 20.

As seen in FIG. 4A, each of the sensors 24 characterizes the tissue 44,generally within a hemisphere-like volume 48, adjacent to it.

As seen in FIG. 4B, where the element 20 is shaped as a truncated cone,the sensors 24 may also be arranged along the base 26.

The at least one sensor 24 may be an irradiative sensor, such as anoptical sensor, an X-ray sensor, an RF sensor, a MW sensor, an infraredthermography sensor, or an ultrasound sensor. Additionally oralternatively, the at least one sensor 24 may be an MR sensor, animpedance sensor, a temperature sensor, a biosensor, a chemical sensor,a radioactive-emission sensor, a mechanical sensor, a nonirradiative RFsensor, for example, as taught by commonly owned U.S. Patent Application60/665,842, filed on Mar. 29, 2005, whose disclosure is incorporatedherein by reference, and (or) another tissue characterization sensor, asknown.

FIG. 5 schematically illustrates a method 90 for soft tissuecharacterization, by improving a contact level between the soft tissue44 and the at least one sensor 24, in accordance with some embodimentsof the present invention. The method 90 includes:

-   in a box 92: arranging at least one sensor for the characterization    of a soft tissue on a rigid surface, having a linear cross section;-   in a box 94: applying a force to the soft tissue at an acute angle    to the rigid surface of the linear cross section, thus stretching or    stretching and pushing the soft tissue against the rigid surface,    and achieving effective contact between the sensor and the tissue;    and-   in a box 96: performing measurements with the at least one sensor.

Referring further to the drawings, FIGS. 6A-6F schematically illustratearrangements of a plurality of the sensors 24 in the device 10, foryielding three-dimensional information, for example, by small-scalecomputerized tomography, in accordance with some embodiments of thepresent invention.

As seen in FIGS. 6A and 6B, the element 20 may be formed as a circularstructure 20, such as the cone 20, with the plurality of the sensors 24,preferably arranged in circles around the internal circumference,embedded within or mounted on the rigid surface 22. Preferably, thesensors 24 of each circle are substantially aligned, along the verticalaxis for example, forming a line 24C (FIG. 6B).

The sensors 24 are adapted for small-scale computerized tomography,which may be transmission small-scale computerized tomography,reflection small-scale computerized tomography, or a combination of thetwo. Preferably, each of the sensors 24, around the circumference, inturn, operates as a transmitting sensor 24A, sending out a signal 23,while the other sensors 24 operate as receiving sensors 24B, receivingsignals 27 which may be transmitted, reflected, or a combination oftransmitted and reflected. The position of the transmitting sensor 24Amay change, for example by rotation, in a direction of an arrow 25.Alternatively, the position of the transmitting sensor 24A may change inanother fashion, for example, randomly. In accordance with an embodimentof the present invention, the transmitting sensors 24A are aligned alongthe vertical line 24C, so as to image “slices of tissue.”

It will be appreciated that other arrangements are similarly possible.For example, two or more sensors 24 in a circle may operate astransmitters, or as transmitters and receivers, at a given time.

It will be appreciated that, depending on the modality, the transmittingsensor may also operate as a receiving sensor. For example, anultrasound transducer may operate both as a transmitter and receiver.Similarly, an optical-fiber end may operate as both, for example, asillustrated in conjunction with FIG. 10B, hereinbelow. Yet, for x-rayCT, dedicated transmitters and receivers may be used.

As seen in FIG. 6C, the sensors 24 may be randomly spread, and any onesensor 24 may operate as a transmitting sensor, or as a transmitting andreceiving sensor, at any one time. The associated algorithm provides thethree-dimensional information, for the specific arrangement.

FIGS. 6D-6F illustrate configurations that may be used to provide athree dimensional image of a tissue voxel of the tissue 44.

As seen in FIG. 6D, the sensor 24 has a viewing angle β.

As seen in FIG. 6E, when several sensors 24, such as sensor 24D, 24E,and 24F, are arranged along the element 20, formed as a flat plate:

the tissue voxel 44 x is not viewed by any of the sensors;

the tissue voxel 44 i is viewed only by the sensor 24D;

the tissue voxel 44 j is viewed by both the sensors 24D and 24E; and

the tissue voxel 44 k is viewed by the three sensors 24D, 24E and 24F.

As illustrated, some three dimensional information may be obtained forthe voxels 44 j and 44 k.

Alternatively, as seen in FIG. 6F, when several sensors 24, such assensor 24G, 24H, 24I, and 24J, are arranged along the element 20, formedas a cone or a cylinder:

the tissue voxel 44 u is viewed by all the four sensors, 24G, 24H, 24I,and 24J;

the tissue voxel 44 v is viewed by the three sensors, 24G, 24H, and 24J;and

the tissue voxel 44 w is viewed by the two sensors, 24I and 24J.

Thus, in the configuration of FIG. 6F, some three dimensionalinformation may be obtained for all the tissue voxels.

Naturally, a shape with a curvature, such as a circular or ellipticalarrangement or a section thereof is preferred to the flat platearrangement. Nonetheless, the flat plate arrangement does yield somethree-dimensional information, and is within the scope of the presentinvention.

It will be appreciated that, while effective contact is highlydesirable, the three-dimensional information may be achieved alsowithout effective contact, thus without the mechanism for applying theforce to the tissue, with the line of force at the acute angle α to thelinear rigid surface 22, as described in conjunction with FIGS. 1A-1V.Hence shapes that do not meet this criterion may nonetheless be used forthe small-scale computerized tomography.

While the shapes illustrated in FIGS. 1O, 1P, 1Q, 1S, 1T, and 1U are themost preferred, since they provide both effective contact and curvature,other shapes may also be used, as illustrated in FIGS. 6G-6N.

FIGS. 6G-6M schematically illustrate elements 20A, shaped with acurvature, which may be round, oval, or of another shape, for providingthe three-dimensional information, but without necessarily providing theeffective contact. These may include a cylinder (FIGS. 6G and 6K), ahalf an egg-like shape (FIGS. 6H and 6L), a semi sphere (FIG. 6J), and abarrel shape (FIGS. 6I and 6M). It will be appreciated that many othershapes are also possible.

A curvature may be defined, vis a vis FIG. 6N, as the ratio of anaverage change in the angles δ(1), δ(2), δ(3), . . . of a tangent thatmoves over a given arc 20B to the length of the arc t.

Preferably, the curvature of the element 20A is at least greater thanthat of a circle having a diameter of 8 cm. Moreover, the curvature ofthe element 20A may be at least greater than that of a circle having adiameter of 6 cm. Furthermore, the curvature of the element 20A may beat least greater than that of a circle having a diameter of 4 cm.Additionally, the curvature of the element 20A may be at least greaterthan that of a circle having a diameter of 2 cm. Moreover, the curvatureof the element 20A may be at least greater than that of a circle havinga diameter of 1 cm. Furthermore, the curvature of the element 20A may beat least greater than that of a circle having a diameter of 0.8 cm.Greater curvatures still may also be possible.

The sensors of FIGS. 6A-6N for providing three-dimensional informationmay be irradiative sensors, such as optical sensors, X-ray sensors, RFsensors, MW sensors, infrared thermography sensors, and ultrasoundsensors. Additionally, or alternatively, the sensors may be mechanicalsensors, MR sensors, impedance sensors, nonirradiative RF sensors,radioactive-emission sensors arranged for SPECT, radioactive-emissionsensors arranged for PET, and (or) other tissue characterizationsensors, as known. It will be appreciated that other sensors may beused, for example, biosensors or chemical sensors, for providing surfaceinformation at different points along the tissue 44, without providingvolumetric three-dimensional information.

FIG. 6-O is a flowchart illustrating a method 130 of tissuecharacterization, with small-scale computerized tomography, forobtaining three-dimensional information of a volumetric region of thetissue, in accordance with some embodiments of the present invention.The method 130 includes:

-   in a box 132: arranging at least two sensors for tissue    characterization on a curved surface, so that the at least two    sensors view a same volumetric region of the tissue;-   in a box 134: performing measurements with the at least two sensors;    and-   in a box 136: analyzing the measurements to obtain the    three-dimensional information of the volumetric region.

Referring further to the drawings, FIGS. 7A-7C schematically illustratea device 100 for effective contact, in accordance with an embodiment ofthe present invention. FIGS. 7A-7C are based on a method taught bycommonly owned U.S. patent application Ser. No. 11/196,732, filed onAug. 4, 2005, whose disclosure is incorporated herein by reference. Yet,as described here, the device 100 has a substantially conical structure125, configured for making contact with the tissue. It will beappreciated that the device may be elliptical or circular in crosssection. The conical structure 125 may be, for example, as described inFIG. 1O, transversely, and in FIG. 1S, longitudinally.

The conical structure 125 defines an effective diameter 123 in a firstdirection and a longitudinal axis 121 in a second direction. Thus, theconical structure 125 is curved in the first direction and has a linearcross section in the second direction.

The device 100 operates by two mechanisms, as follows:

a mechanism, which exerts a force F on the tissue 44, in the seconddirection, along the longitudinal axis 121, for fixing the tissue 44against the device 100, so as to substantially immobilize the tissue 44;and

a counter mechanism, which presses the at least one piston sensor 24,associated with it, against the immobilized tissue 44, by exerting acounter force F_(c) in opposition to at least a component of the forceF, thus achieving effective contact between the surface 44 and the atleast one piston sensor 24.

As a first step, seen in FIGS. 7A-7B, the mechanism for the force F isprovided by a vacuum line 116, for creating suction in the conicalstructure 125 (FIG. 7A), thus sucking the tissue 44 towards the rigidsurface 22 of the conical cross section (FIG. 7B).

The longitudinal axis 121 defines a line of force for the force F, atthe acute angle α to the rigid surface 22 of the linear cross section,the linear cross section being in the direction of the line of force(the second direction).

As a second step, seen in FIG. 7C, the counter mechanism, for thecounter force F_(c) in opposition to the force F, is provided by thepiston 120, moving in the direction of an arrow 120, and pressing the atleast one piston sensor 24 into the immobilized tissue 44, thusachieving affective contact between the at least one piston sensor 24and the portion of the immobilized tissue 44 in contact with the atleast one piston sensor 24.

Seals 115 between the piston 120 and the inner walls 122 of the device100 ensure the vacuum in the vacuum line 116.

It will be further appreciated that one or several cone sensors 24M maybe mounted on the rigid surface 22, arranged so as to provide threedimensional information of the tissue 44.

Thus, the cone sensors 24M will enjoy the effective contact formed bythe force F at the acute angle α to the rigid surface 22 of the linearcross section (FIG. 7A), for stretching or stretching and pushing thetissue 44 against the rigid surface 22. Yet, the cone sensors 24M willnot benefit from the second mechanism, of the piston 120, which pushesthe at least one piston sensor 24 against the tissue 44, with the forceF_(C), seen in FIG. 7C.

The at least one piston sensor 24 and the at least one cone sensor 24Mmay be optical sensors, X-ray sensors, RF sensors, MW sensors, infraredthermography sensors, ultrasound sensors, MR sensors, impedance sensors,temperature sensors, biosensors, chemical sensors, radioactive-emissionsensors, mechanical sensors, nonirradiative RF sensors, or any othertissue characterization sensor, as known.

Referring further to the drawings, FIGS. 7D-7F schematically illustrateanother configuration for effective contact, in accordance with anotherembodiment of the present invention, wherein a sensor 24 is located onthe piston 120, but no cone sensors 24M are used.

Again, the line of force for the force F is at the acute angle α to therigid surface 22 of the linear cross section of the conical structure125, fixing the tissue 44 to the rigid surface 22.

As a second step, seen in FIG. 7F, the counter mechanism, for thecounter force F_(c) in opposition to the force F, is provided by thepiston 120, moving in a direction of an arrow 120A, and pressing the atleast one piston sensor 24 into the immobilized tissue 44, achievingaffective contact between the piston sensor 24 and the portion of theimmobilized tissue 44 in contact with the piston sensor 24.

FIGS. 7G-7H schematically illustrate configurations with several typesof sensors, in accordance with embodiments of the present invention.

As seen in FIG. 7G, three types of sensors may be used, cone sensors 24Xand 24Y along the conical structure 125, and a piston sensor 24Z on thepiston 120. This arrangement will provide three-dimensional informationby both the cone sensor types 24X and 24Y. In this manner,three-dimensional information for example, by ultrasound and opticalsensors, or by MRI and X-ray may obtained and compared. It will beappreciated that many combinations of mixed sensor types are possible.

It will be noted that the piston sensor 24Z is arranged so as not toprovide three-dimensional information.

As seen in FIG. 7H, two types of sensors are used, 24X and 24Y,scattered on the rigid surface 22. This arrangement will again providethree-dimensional information by the sensors 24X and 24Y. Again,three-dimensional information of different modalities may be obtainedand compared.

The sensors 24X, 24Y, and 24Z may be, for example, irradiative sensors,such as optical sensors, X-ray sensors, RF sensors, MW sensors, infraredthermography sensors, ultrasound sensors, or nonirradiative sensors,such as MR sensors, impedance sensors, temperature sensors, biosensors,chemical sensors, radioactive-emission sensors, mechanical sensors,nonirradiative RF sensors, or other sensors as known.

FIG. 8 schematically illustrates a first sensor construction 74 for thedevice 10, in accordance with some embodiments of the present invention.The first sensor construction 74 is applicable to sensors 24, whereineach is operative as both a transmitter and a receiver.

Alternatively, the first sensor construction 74 is applicable to sensors24, operative as receivers of natural signals, for example, bodytemperature sensors, where no transmission is necessary.

Accordingly, the first sensor construction 74 includes the signalgenerator and analyzer 60, the signal communication line 16 to eachsensor, and the sensors 24, each operative as a transmitter and areceiver.

FIG. 9 schematically illustrates a second sensor construction 75, forthe device 10, where a sensor 24A is a transmitter and a sensor 24B is areceiver, in accordance with some embodiments of the present invention.Accordingly, the second sensor construction 75 includes the signalgenerator and analyzer 60, signal communication lines 16A to eachtransmitting sensor 24A, and receiving lines 16B, from each receivingsensor 24B.

FIGS. 10A and 10B schematically illustrate optical sensor constructionsfor the device 10, in accordance with some embodiments of the presentinvention.

In accordance with one embodiment, seen in FIG. 10A, an optical sensorconstruction 76 includes optical signal generators 60A, such as lasersor LEDs, and optical signal analyzers 60B, formed, for example, as CCDs.The signal communication lines 16 include optical fibers 16A leadingfrom the optical signal generators 60A to the tissue and optical fibers16B, leading from the tissue to the optical signal analyzers 60B. Thesensors 24 are the proximal endings of the optical fibers 16A and 16B,with respect to the tissue.

In accordance with another embodiment, seen in FIG. 10B, an opticalsensor construction 78 includes the optical signal generators 60A, suchas the lasers or the LEDs, and the optical signal analyzers 60B, forexample, formed as the CCDs. The signal communication lines 16 includeoptical fibers leading both from the optical signal generators 60A tothe tissue and from the tissue to the optical signal analyzers 60B. Beamsplitters 60C, at the distal end with respect to the tissue, direct thebeam from the optical signal generators 60A to the optical fibers 16 andfrom the optical fibers 16 to the optical signal analyzers 60B. Thesensors 24 are the proximal endings of the optical fibers 16, withrespect to the tissue. Other techniques for using a single optical fiberboth for transmitting and for receiving optical signals may also beused.

It will be appreciated that another signal communication architecturemay be used, as known.

In accordance with some embodiments of the present invention, tissuecharacterization may be performed by various techniques, including anyone from the following nonexhaustive list.

Tissue Characterization by Ultrasonography:

Ultrasonography is a medical imaging technique, using high frequencysound waves in the range of about 1 to 40 MHz and their echoes. Thesound waves travel in the body and are reflected by interfaces betweendifferent types of tissues, such as between a healthy tissue and adenser, cancerous tissue, or between a portion of a soft tissue and abone. The ultrasound probe receives the reflected sound waves and theassociated instrumentation calculates the distances from the probe tothe reflecting boundaries.

The ultrasound probe includes a piezoelectric crystal, which produces anelectric signal in response to a pressure pulse. The shape of the probedetermines its field of view, and the frequency of the emitted sounddetermines the minimal detectable object size. Generally, the probes aredesigned to move across the surface of the body. However, some probesare designed to be inserted through body lumens, such as the vagina orthe rectum, so as to get closer to the organ being examined.

Before the early 1970's ultrasound imaging systems were able to recordonly the strong echoes arising from the outlines of an organ, but notthe low-level echoes of the internal structure. In 1972 a refinedimaging mode was introduced called gray-scale display, in which theinternal texture of many organs became visible. In consequence,ultrasound imaging became a useful tool for imaging tumors, for example,in the liver.

A development of recent years is a 3D ultrasound imaging, in whichseveral two-dimensional images are acquired by moving the probes acrossthe body surface or by rotating probes, inserted into body lumens. Thetwo-dimensional scans are then combined by specialized computer softwareto form 3D images.

In multiple-element probes, each element has a dedicated electriccircuit, so that the beam can be “steered” by changing the timing inwhich each element sends out a pulse. By sequentially stimulating eachelement, the beams can be rapidly steered from the left to right, toproduce a two-dimensional cross-sectional image. Additionally,transducer-pulse controls allow the operator to set and change thefrequency and duration of the ultrasound pulses, as well as the scanmode of the machine. A probe formed of array transducers has the abilityto be steered as well as focused.

Contrast agents may be used in conjunction with ultrasound imaging, forexample as taught by U.S. Pat. No. 6,280,704, to Schutt, et al.,entitled, “Ultrasonic Imaging System Utilizing a Long-PersistenceContrast Agent,” whose disclosure is incorporated herein by reference.

Tissue Characterization by its Dielectric Properties:

There are several known techniques for local tissue characterization bythe tissue's electromagnetic properties.

Commonly owned U.S. Pat. No. 6,813,515, to Hashimshony, entitled,“Method and System for Examining Tissue According to the DielectricProperties Thereof,” whose disclosure is incorporated herein byreference, describes a method and system for examining tissue in orderto differentiate it from other tissue, according to the dielectricproperties of the examined tissue. The method includes applying anelectrical pulse to the tissue to be examined via a probe formed with anopen cavity such that the probe generates an electrical fringe field inexamined tissue within the cavity and produces a reflected electricalpulse therefrom with negligible radiation penetrating into other tissuesor biological bodies near the examined tissue; detecting the reflectedelectrical pulse; and comparing electrical characteristics of thereflected electrical pulse with respect to the applied electrical pulseto provide an indication of the dielectric properties of the examinedtissue.

Furthermore, commonly owned U.S. Patent Application 60/641,081,entitled, “Device and Method for Tissue Characterization in a BodyLumen, by an Endoscopic Electromagnetic Probe,” whose disclosure isincorporated herein by reference, discloses a device and method fortissue characterization in a body lumen, for the detection ofabnormalities, using an electromagnetic probe mounted on an endoscope.The endoscope may be designed for insertion in a body lumen, selectedfrom the group consisting of an oral cavity, a gastrointestinal tract, arectum, a colon, bronchi, a vagina, a cervix, a urinary tract, and bloodvessels. Additionally, it may be designed for insertion in a trocarvalve.

Additionally, commonly owned U.S. Patent Application 60/665,842,entitled, “Electromagnetic Sensors for Tissue Characterization,” whosedisclosure is incorporated herein by reference, discloses a sensorcomprising: a resonating element, formed as a conductive structure,configured to be placed proximally to an edge of a tissue forcharacterization, without penetrating the tissue. The resonating elementhas a diameter-equivalent D, which defines a cross-sectional areathereof, on a plane substantially parallel with the edge, and at leastone conductive lead, for providing communication with an externalsystem, wherein the resonating element is configured to resonate at afree-air wavelength range of between about λ and about 10λ, wherein λ isat least about ten times the diameter-equivalent D. Upon receiving asignal in the range of between about λ and about 10λ, the sensor isconfigured to induce electric and magnetic fields, in a near zone, inthe tissue, the near zone being a hemisphere having a diameter ofsubstantially D, beginning with the edge, while causing negligibleradiation in a far zone, so that the tissue, in the near zone,effectively functions as part of the resonating element, varying aresonating response to the sensor, and so the tissue, in the near zone,is thereby characterized by its electromagnetic properties, by theresonating response to the sensor.

Tissue Characterization by Electrical Impedance Imaging:

Electrical impedance imaging relates to measuring the impedance betweena point on the surface of the skin and some reference point on the bodyof a patient. Sometimes, a multi-element probe, formed as a sheet havingan array of electrical contacts, is used for obtaining a two-dimensionalimpedance map of the tissue, for example, the breast. Thetwo-dimensional impedance map may be used, possibly in conjunction withother data, such as mammography, for the detection of cancer.

Rajshekhar, V. (“Continuous Impedance Monitoring During CT-GuidedStereotactic Surgery Relative Value in Cystic and Solid Lesions,”Rajshekhar, V., British Journal of Neurosurgery, 1992, 6, 439-444)describes using an impedance probe with a single electrode to measurethe impedance characteristics of lesions. The objective of the study wasto use the measurements made in the lesions to determine the extent ofthe lesions and to localize the lesions more accurately. The probe wasguided to the tumor by CT and four measurements were made within thelesion as the probe passed through the lesion. A biopsy of the lesionwas performed using the outer sheath of the probe as a guide toposition, after the probe itself was withdrawn.

U.S. Pat. No. 4,458,694, to Sollish, et al., entitled, “Apparatus andMethod for Detection of Tumors in Tissue,” whose disclosure isincorporated herein by reference, relates to an apparatus for detectingtumors in human breast, based on the dielectric constants of localizedregions of the breast tissue. The apparatus includes a probe, includinga plurality of elements. The apparatus further includes means forapplying an AC signal to the tissue, means for sensing dielectricproperties at each of the probe elements at different times, and signalprocessing circuitry, coupled to the sensing means, for comparing thedielectric properties sensed at the different times. The apparatus thusprovides an output of the dielectric constants of localized regions ofbreast tissue associated with the probe.

Similarly, U.S. Pat. No. 4,291,708 to Frei, et al., entitled, “Apparatusand Method for Detection of Tumors in Tissue,” whose disclosure isincorporated herein by reference, relates to apparatus for detectingtumors in human breast tissue, by the dielectric constants of aplurality of localized regions of human breast tissue.

U.S. Pat. Nos. 6,308,097; 6,055,452; and 5,810,742, to Pearlman, A. L.,entitled, “Tissue Characterization Based on Impedance Images and onImpedance Measurements,” whose disclosures are incorporated herein byreference, describe apparatus for aiding in the identification of tissuetype for an anomalous tissue in an impedance image. The devicecomprises: means for providing a polychromic emmitance map of a portionof the body; means for determining a plurality of polychromic measuresfrom one or more portions of the body; and a display of an indicationbased on the plurality of polychromic measures.

Tissue Characterization by Optical Fluorescence Spectroscopy:

When a sample of large molecules is irradiated, for example, by laserlight, it will absorb radiation, and various levels will be excited.Some of the excited states will revert back substantially to theprevious state, by elastic scattering, and some energy will be lost ininternal conversion, collisions and other loss mechanisms. However, someexcited states will create fluorescent radiation, which, due to thedistribution of states, will give a characteristic wavelengthdistribution.

Some tumor-marking agents give well-structured fluorescence spectra,when irradiated by laser light. In particular, hematoporphyrinderivatives (HPD), give a well-structured fluorescence spectrum, whenexcited in the Soret band around 405 nm. The fluorescence spectrum showstypical peaks at about 630 and 690 nm, superimposed in practice on moreunstructured tissue autofluorescence. Other useful tumor-marking agentsare dihematoporphyrin ether/ester (DHE), hematoporphyrin (HP),polyhematoporphyrin ester (PHE), and tetrasulfonated phthalocyanine(TSPC), when irradiated at 337 nm (N₂ laser).

U.S. Pat. No. 5,115,137, to Andersson-Engels, et al., entitled,“Diagnosis by Means of Fluorescent Light Emission from Tissue,” whosedisclosure is incorporated herein by reference, relates to improveddetection of properties of tissue by means of induced fluorescence oflarge molecules. The tissue character may then be evaluated from theobserved large-molecule spectra. According to U.S. Pat. No. 5,115,137,the spectrum for tonsil cancer is clearly different from that of normalmucosa, due to endogenous porphyrins.

U.S. Pat. No. 6,258,576, to Richards-Kortum, et al., entitled,“Diagnostic Method and Apparatus for Cervical Squamous IntraepithelialLesions In Vitro and In Vivo Using Fluorescence Spectroscopy,” whosedisclosure is incorporated herein by reference, relates to the use ofmultiple illumination wavelengths in fluorescence spectroscopy for thediagnosis of cancer and precancer, for example, in the cervix. In thismanner, it has been possible to (i) differentiate normal or inflamedtissue from squamous intraepithelial lesions (SILs) and to (ii)differentiate high grade SILs from non-high grade SILs. The detectionmay be performed in vitro or in vivo. Multivariate statistical analysishas been employed to reduce the number of fluorescenceexcitation-emission wavelength pairs needed to re-develop algorithmsthat demonstrate a minimum decrease in classification accuracy. Forexample, the method of the aforementioned patent may compriseilluminating a tissue sample with electromagnetic radiation wavelengthsof about 337 nm, 380 nm and 460 nm, to produce fluorescence; detecting aplurality of discrete emission wavelengths from the fluorescence; andcalculating from the emission wavelengths a probability that the tissuesample belongs in particular tissue classification.

Commonly owned U.S. Patent Application 2003/0138378, to Hashimshony,entitled, “Method and Apparatus for Examining Tissue for PredefinedTarget Cells, Particularly Cancerous Cells, and a Probe Useful for SuchMethod and Apparatus,” whose disclosure is incorporated herein byreference, teaches a method, apparatus, and probe for examining tissueand characterizing its type according to measured changes in opticalcharacteristics of the examined tissue. In a preferred embodiment ofthis method the tissue to be examined is subject to a contrast agentcontaining small particles of a physical element conjugated with abiological carrier selectively bindable to the target cells.Additionally, energy pulses are applied to the examined tissue, and thechanges in impedance and/or the optical characteristics produced by theapplied energy pulses are detected and utilized for determining thepresence of the target cells in the examined tissue. Furthermore, in apreferred embodiment, the applied energy pulses include laser pulses,and the physical element conjugated with a biological carrier is alight-sensitive semiconductor having an impedance which substantiallydecreases in the presence of light. Moreover, the same probe used fordetecting the targeted cells, may also be used for destroying the cellsso targeted.

Tissue Characterization by Optical Reflectance Spectroscopy:

The application optical reflectance spectroscopy for tissuecharacterization is described, for example, inwww.sbsp-limb.nichd.nih.gov/html/spectroscopy.html, downloaded on Mar.15, 2005, disclosing an optical reflectance spectroscopy (ORS) devicefor measuring the thickness of the epithelial layer, and an evaluationtechnique based on oblique angle reflectance spectroscopy, that allowsassessment of the scattering and absorption properties of the epitheliumand stroma, thus providing information on chronic oral epithelial tissueinflammation, which is considered a potential diagnostic precursor tooral cancer.

Additionally, Tomatis, A., et al., studied reflectance images of 43pigmented lesions of the skin (18 melanomas, 17 common melanocytic naeviand eight dysplastic naevi). Reflectance images were acquired by atelespectrophotometric system and were analyzed in the spectral rangefrom 420 to 1040 nm, to discriminate melanoma from benign melanocyticentities. Different evaluations were carried out considering the wholespectrum, the visible and the near infrared. A total of 33 (76.7%)lesions were correctly diagnosed by the telespectrophotometric system,compared with 35 (81.4%) correct clinical diagnoses. Reflectance in theinfrared band appears diagnostically relevant.

Tissue Characterization by Magnetic Resonance (MR):

Magnetic resonance is based on the absorption and emission of energy inthe radio frequency range of the electromagnetic spectrum, by nucleihaving unpaired spins. Magnetic Resonance Imaging (MRI) is based on theimaging of the absorption and emission of energy in the radio frequencyrange of the electromagnetic spectrum, by nuclei having unpaired spins.

Conventional MRI utilizes a large-apparatus, for whole body imaging,having:

i. a primary magnet, which produces the B_(o) field for the imagingprocedure;

ii. gradient coils for producing a gradient in B_(o);

iii. an RF coil, for producing the B₁ magnetic field, necessary torotate the spins by 90° or 180° and for detecting the MR signal; and

iv. a computer, for controlling the components of the MR imager.

Generally, the magnet is a large horizontal bore superconducting magnet,which provides a homogeneous magnetic field in an internal region withinthe magnet. A patient or object to be imaged is usually positioned inthe homogeneous field region located in the central air gap for imaging.A typical gradient coil system comprises an anti-Helmholtz type of coil.These are two parallel ring-shaped coils, around the z axis. Current ineach of the two coils flows in opposite directions creating a magneticfield gradient between the two coils.

The RF coil creates a B₁ field, which rotates the net magnetization in apulse sequence. The RF coils may be: 1) transmit and receive coils, 2)receive only coils, or 3) transmit only coils.

As described hereinabove, the MRI relies on a magnetic field in aninternal region within the magnet. As such, it is unsuitable as ahandheld probe or an endoscopic probe, because the tissue to be imagedhas to be in the internal region of the imager.

However, U.S. Pat. No. 5,572,132, to Pulyer, et al., entitled, “MRIProbe for External Imaging,” whose disclosure is incorporated herein byreference, describes an MRI spectroscopic probe having an externalbackground magnetic field B₀ (as opposed to the internal backgroundmagnetic field of the large horizontal bore superconducting magnet).Thus, an MRI catheter for endoscopical imaging of tissue of the arterywall, rectum, urinal tract, intestine, esophagus, nasal passages, vaginaand other biomedical applications may be constructed. The probecomprises (i) a miniature primary magnet having a longitudinal axis andan external surface extending in the axial direction, and (ii) an RFcoil surrounding and proximal to the surface. The primary magnet isstructured and configured to provide a symmetrical, preferablycylindrically shaped, homogeneous field region external to the surfaceof the magnet. The RF coil receives NMR signals from excited nuclei. Forimaging, one or more gradient coils are provided to spatially encode thenuclear spins of nuclei excited by an RF coil, which may be the samecoil used for receiving NMR signals or another RF coil.

Additionally, commonly owned US Patent Application 2005/0021019 toHashimshony, et al., entitled “Method and Apparatus for ExaminingSubstance, Particularly Tissue, to Characterize its Type,” whosedisclosure is incorporated herein by reference, describes a method andapparatus for examining a substance volume to characterize its type, by:applying a polarizing magnetic field through the examined substance;applying RF pulses locally to the examined substance volume such as toinvoke electrical impedance (EI) response signals corresponding to theelectrical impedance of the substance, and magnetic resonance (MR)response signals corresponding to the MR properties of the substance;detecting the EI and MR response signals; and utilizing the detectedresponse signals for characterizing the examined substance volume type.

Contrast agents may be used in conjunction with MRI. For example, U.S.Pat. No. 6,315,981 to Unger, entitled, “Gas Filled Microspheres asMagnetic Resonance Imaging Contrast Agents,” whose disclosure isincorporated herein by reference, describes the use of gas filledmicrospheres as contrast agents for MRI.

Additionally, U.S. Pat. No. 6,747,454, to Belt, entitled, “Array ofCoils for Use in Imaging the Vasculature of a Patient,” whose disclosureis incorporated herein by reference, describes an array of coils,configured for use in imaging the vasculature of a patient.

Furthermore, U.S. Pat. No. 6,677,755, to Belt, et al., “Circuit forSelectively Enabling and Disabling Coils of a Multi-Coil Array,” whosedisclosure is incorporated herein by reference, describes a circuit,used to selectively enable and disable n-coils. The circuit includesn-drivers powered by a current source. Each n-driver includes a pair ofFETs disposed such that a gate of one FET is connected to a gate of theother FET to form a common gate node thereat. The n-drivers are disposedin a totem-pole configuration. The first FET of a first of the n-drivershas (A) a drain linked to a ground and to an end of a first of then-coils and (B) a source linked to a drain of the first FET of a secondof the n-drivers and to an end of a second of the n-coils. The other FETof the first of the n-drivers has (A) a source linked to an opposite endof the first of the n-coils and (B) a drain linked to the end of thesecond of the n-coils and to the source of the first FET of the first ofthe n-drivers. The first FET of the second of the n-drivers also has asource linked to a drain of the first FET of a successive n-driver andto an end of a successive n-coil. The other FET of the second of then-drivers also has (A) a source linked to an opposite end of the secondof the n-coils and (B) a drain linked to the end of the successiven-coil and to the source of the first FET of the second of then-drivers. This continues until the first FET and the other FET of annth of the n-drivers are likewise disposed in the totem-poleconfiguration of the n-drivers, with a source and a drain of the firstFET and the other FET, respectively, of the nth of the n-drivers beingconnected to the current source. Each of the n-drivers is used tooperate a corresponding one of the n-coils by being responsive at itscommon gate node (i) to a coil disable signal by activating the firstFET thereof and deactivating the other FET thereof thereby not onlydrawing current away from and thus disabling the corresponding coil butalso allowing the current to flow through the first FET and thus to beavailable as a source of current to a successive one of the n-driversand (ii) to a coil enable signal by deactivating the first FET thereofand activating the other FET thereof thereby allowing the current notonly to flow serially through the corresponding coil and the other FETthus enabling the corresponding coil but also to be available as asource of current to the successive one of the n-drivers.

Tissue Characterization by Magnetic Resonance Spectroscopy (MRS):

In MRS, spectroscopic NMR data is obtained from the examined area. Thusthe biochemical information obtained from MRS can be interpreted inrelation to a defined anatomical location, and images of metabolitedistributions can be generated. MRS can be used to identify surrogatebiochemical markers of cellular transformation, thus differentiatingbenign tumors from malignant ones, and identifying different tumortypes. Prognostic and diagnostic information is derived from thespectrum of malignant tumors (Breast Cancer Res. 2001, 3:36-40).

Tissue Characterization by Radioactive Emission:

Radioactive-emission imaging relies on the fact that, in general,pathologies, such as malignant tumors and inflammations, display a levelof activity different from that of healthy tissue. Thus,radiopharmaceuticals, which circulate in the blood stream, are picked upby the active pathologies to a different extent than by the surroundinghealthy tissue; in consequence, the pathologies are operative asradioactive-emission sources and may be detected by radioactive-emissionimaging.

The pathological feature may appear as a concentrated source of highradiation, or a hot region, as may be associated with a tumor, or as aregion of low-level radiation, which is nonetheless above the backgroundlevel, as may be associated with carcinoma. Additionally, a reversedsituation is possible. Dead tissue has practically no pick up ofradiopharmaceuticals, and is thus operative as a region of littleradiation, or a cold region, below the background level.

Thus radiopharmaceuticals may be used for identifying active pathologiesas well as dead tissue, and the image that is constructed is generallytermed, a “functional image.”

The mechanism of localization of a radiopharmaceutical depends onvarious processes in the organ of interest, such as antigen-antibodyreactions, physical trapping of particles, receptor site binding,removal of intentionally damaged cells from circulation, and transportof a chemical species across a cell membrane and into the cell by anormally operative metabolic process. A summary of the mechanisms oflocalization by radiopharmaceuticals is found inwww.lunis.luc.edu/nucmed/tutorial/radpharm/i.htm.

The particular choice of a radionuclide for labeling antibodies dependsupon the chemistry of the labeling procedure and the isotope nuclearproperties, such as, the number of gamma rays emitted, their respectiveenergies, the emission of other particles, such as beta or positrons,the isotope half-life, and the existence of different isotopes ofidentical chemistry but different half-lives (e.g., I¹³¹ and I¹³³). Theusual preferred emission for medical applications is that of gamma rays.However, beta and positron radiation may also be detected, and are ofparticular relevance in PET imaging.

The sensor may be a room temperature, solid-state CdZnTe (CZT) detector,configured as a single-pixel or a multi-pixel detector. Alternatively,another solid-state detector such as CdTe, HgI, Si, Ge, or the like, ora scintillation detector, such as NaI(Tl), LSO, GSO, CsI, CaF, or thelike, or a combination of scintillation materials and photodiode arraysmay be used.

Two technologies of computed tomography for radioactive emission areknown.

i. Single photon emission computed tomography (SPECT), in which singleradioactive emission events are detected around a body. The detection ofa large number of photons may be used to form a three-dimensionalfunctional image and thus identify the source of the radiation.

ii. Positron emission tomography (PET), in which a positron is emittedfrom the radioactive isotope. Upon its interaction with an electron,annihilation occurs, and the two photons produced by the annihilationtravel in opposite directions. Their detection by coincidence countingidentifies an exact path upon which the annihilation took place. Again,the detection of a large number of photons may be used to form athree-dimensional functional image and identify the source of theradiation, especially using the fact that in PET, the photon paths forcoincidence counts are known,

Attenuation by the surrounding tissue introduces a certain error.

Various radiopharmaceuticals can be synthesized to target specificmolecules present in the target tissue cells, for example, [¹⁸F] FDG(fluorodeoxyglucose), or antibody fragment labeled with [⁶⁴Cu]. Othersmay be found inwww.crump.ucla.edu/software/lpp/radioisotopes/tracers.html. Additionaldetails and descriptions may be found in Breast Cancer Res. 2001,3:28-35.

Tissue Characterization by Temperature Imaging:

Temperature imaging for locating and detecting neoplastic tissue hasbeen known since the 1950's, when it was discovered that the surfacetemperature of skin in the area of a malignant tumor exhibited a highertemperature than that expected of healthy tissue. Thus, by measuringbody skin temperatures, it became possible to screen for the existenceof abnormal body activity such as cancerous tumor growth. With thedevelopment of liquid crystals and methods of forming temperatureresponsive chemical substrates, contact thermometry became a realityalong with its use in medical applications. Devices employing contactthermometry could sense and display temperature changes throughindicators which changed colors, either permanently or temporarily, whenplaced in direct physical contact with a surface such as skin,reflecting a temperature at or near the point of contact. An abnormalreading would alert a user to the need for closer, more detailedexamination of the region in question. However, the art in this area hasbeen directed primarily at sensing and displaying temperatures onexterior skin surfaces.

U.S. Pat. No. 3,830,224, to Vanzetti, et al., whose disclosure isincorporated herein by reference, discloses the placement of temperatureresponsive, color changing liquid crystals at various points in abrassiere for the purpose of detecting the existence of breast cancer.

U.S. Pat. RE 32,000, to Sagi, entitled, “Device for Use in EarlyDetection of Breast Cancer,” whose disclosure is incorporated herein byreference, discloses a device comprising a flexible, heat-conductiveweb, preferably in the form of a disc-shaped patch having an adhesivelayer on one side thereof and a peelable layer removably secured theretoby the adhesive layer. On the other side thereof, the device comprisesan array of spaced-apart indicators, each of the indicators comprising adye or a pigment and a temperature sensitive substance (crystallineorganic chemical) which melts at a relatively precise temperature whichis approximately 0.5 degree. F different from the adjacent indicator. Asmany indicators are used as are necessary to cover the desiredtemperature range. The device is incorporated into the breast-receivingcups of a brassiere and mirror image quadrants of the two breasts arescanned and the device is visually examined to determine the number ofindicators which have displayed a change in color, thus apprising theperson of the existence of abnormality in the mammary tissue.

U.S. Pat. No. 6,135,968, to Brounstein, entitled, “DifferentialTemperature Measuring Device and Method”, whose disclosure isincorporated herein by reference, describes a device and method forsensing temperatures at internal body locations non-surgicallyaccessible only through body orifices. The device is particularly usefulin medical applications such as screening for cancer and other abnormalbiological activity signaled by an increase in temperature at a selectedsite. As applied to prostate examinations, the device is temporarily,adhesively affixed to a user's fingertip or to a mechanical probe. Inthe preferred embodiment, the device includes two temperature-sensingelements, which may include a plurality of chemical indicators. Eachindicator changes color in response to detection of a predeterminedparticular temperature. When properly aligned and installed, the firstelement is located on the palmar surface of the fingertip while thesecond element is located on the dorsal surface of the fingertip. Afteran examination glove has been donned over the fingertip carrying thedevice, a prostate examination is performed during which the firstelement is brought into constant but brief contact with the prostateregion and the second element is similarly, simultaneously brought intocontact with a dermal surface opposing the prostate region. Uponwithdrawal of the fingertip from the rectum and removal of the glove,the two temperature sensing elements may be visually examined in orderto determine the temperatures detected by each one. A significantdifference in observed temperatures indicates the possibility ofabnormal biological activity and the need for further diagnostic ormedical procedures.

Tissue Characterization Using Biosensors:

Biosensors may be of catalytic type such as integrated enzymes, cellularorganelles, tissues or whole microorganisms with transducers thatconvert a biological response into a digital electronic signal. Theprincipal transducers used are electrochemical, optical, orthermometric. Biosensors may also be of affinity type. Affinitybiosensors deliver information about the binding of antibodies toantigens, cell receptors to their ligands, and DNA and RNA to nucleicacid with a complementary sequence. Still, additional types are fullyintegrated biochip devices that perform as micro bio-reactors. All typescan be used in high-density arrays of bio-molecular sensors.

Some of these sensors are further discussed in:

(i) Enzyme and Microbial Biosensors: Techniques and Protocols, A.Mulchandani & K. R. Rogers (Humana Press, 1998);

(ii) Affinity Biosensors: Techniques and Protocols, A. Mulchandani & K.R. Rogers (Humana Press, 1998);

(iii) Journal: Biosensors & Bioelectronics:

-   -   a. Volume 20, Issue 8, Pages 1459-1695 (15 Feb. 2005);    -   b. Volume 20, Issue 6, Pages 1029-1259 (15 Dec. 2004);    -   c. Volume 20, Issue 5, Pages 917-1028 (15 Nov. 2004);    -   d. Volume 20, Issue 1, Pages 1-142 (30 Jul. 2004);    -   e. Volume 20, Issue 12, Pages 2387-2593 (15 Jun. 2005);

(iv) Journal: Sensors & Actuators B (chemical).

-   -   a. Volume 103, Issues 1-2, Pages 1-473 (29 Sep. 2004);    -   b. Volume 102, Issue 1, Pages 1-177 (September 2004); and    -   c. Volume 106, Issue 1, Pages 1-488 (29 Apr. 2005).

Tissue Characterization Using Chemical Sensors:

Chemical sensors detect the presence of various types of chemicalcompounds and states. These include, for example, ions, such as, but notlimited to, Na, K; dissolved gases, such as, but not limited to, oxygen,carbon dioxide; and sensors for determining Ph of solution.

Some of these sensors are further discussed in:

(i) Sensors: A Comprehensive Survey. Volume 2: Chemical and BiochemicalSensors, Part I, W. Gopel, J. Hesse, & J. N. Zemel (VCH, 1991);

(ii) Sensors: A Comprehensive Survey. Volume 3: Chemical and BiochemicalSensors, Part II, W. Gopel, J. Hesse, & J. N. Zemel (VCH, 1992); and

(iii) Journal: Sensors & Actuators B (Chemical):

-   -   a. Volume 103, Issues 1-2, Pages 1-473 (29 Sep. 2004);    -   b. Volume 102, Issue 1, Pages 1-177 (September 2004);    -   c. Volume 108, Issues 1-2, Pages 1-1000 (22 Jul. 2005).

Tissue characterization using mechanical sensors: Mechanical sensorsmeasure a physical property of the tissue in contact with the sensor.One example of a mechanical sensor uses tactile sensing that measuresthe pressure sensed on the sensor surface. An optical tactile sensorhaving a transparent elastic tactile portion has been taught in U.S.Pat. No. 6,909,084 to Tachi and Kajimoto, whose disclosure isincorporated herein by reference. This is an optical tactile sensor witha tactile section and imaging means, the tactile section comprising atransparent elastic body and a plurality of groups of markers providedinside the elastic body, each marker group made up of a number ofcolored markers, with markers making up different marker groups havingdifferent colors for each group, and behavior of the colored markerswhen an object touches the elastic body being photographed by theimaging means. Preferably the marker groups have mutually differentspatial arrangements. Furthermore, mechanical sensors are discussed in:Sensors: A Comprehensive Survey, Volume 7: Mechanical Sensors, W. Gopel,J. Hesse, & J. N. Zemel (VCH, 1994).

It will be appreciated that the method, in accordance with someembodiments of the present invention may adapted for human tissue andfor animal tissue.

It will be appreciated that the probes according to embodiments of thepresent invention may be applied extracorporeally, to the skin.Alternatively, they may be applied to subcutaneous tissue, during opensurgery.

It will be appreciated that the probes according to embodiments of thepresent invention may be insertion intracorporeally, for a minimallyinvasive procedure, having an incision, for example, no greater thanabout 3 centimeters.

Alternatively, they may be inserted to a body lumen.

It is expected that during the life of this patent many relevantbroad-band sensors for tissue characterization will be developed and thescope of the term broad-band sensor for tissue characterization isintended to include all such new technologies a priori.

As used herein the term “about” and “substantially” refer to ±20%.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, any citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention.

What is claimed is:
 1. A device for tissue characterization, comprising:a structure, formed of a rigid surface configured as a truncated cone,having a first cross-sectional configuration defining a diameter andhaving a second cross-sectional configuration defining an axis; at leastone piston sensor; a first force exerting mechanism, associated with thestructure, configured to provide a first force and to cause said firstforce to be exerted on a tissue, in a direction, along the axis, at anacute angle α to the rigid surface, for fixing the tissue to thestructure, so as to immobilize the tissue; and a second force exertingmechanism, associated with the structure, configured to press said atleast one piston sensor against an external surface of the immobilizedtissue thereby to provide a counter force, and to thereby exert saidcounter force on the immobilized tissue, wherein the first forceexerting mechanism is configured to set at least a component of theforce in opposition to at least a component of the counter force, saidstructure, said first mechanism and said second mechanism combined beingconfigured to force the immobilized tissue against the at least onepiston sensor, and further to force the at least one piston sensoragainst the immobilized tissue, bringing about an effective contactbetween the at least one piston sensor and the immobilized tissue; andwherein said at least one piston sensor is selected from the groupconsisting of optical sensor, X-ray sensor, RF sensor, MW sensor,infrared thermography sensor, ultrasound sensor, MR sensor, impedancesensor, temperature sensor, radioactive-emission sensor, mechanicalsensor, and a nonirradiative RF sensor.
 2. The device of claim 1,wherein the at least one piston sensor includes at least two pistonsensors of a same type.
 3. The device of claim 1, wherein the at leastone piston sensor includes at least two piston sensors of differenttypes.
 4. The device of claim 1, and further including at least one conesensor, arranged on the rigid surface.
 5. The device of claim 1, andfurther including at least two cone sensors, arranged on the rigidsurface of the linear cross section.
 6. The device of claim 5, whereinthe at least two cone sensors are arranged along the curvature, eachcone sensor defining a viewing angle, the at least two cone sensorssharing a portion of their viewing angles so as to obtainthree-dimensional information.
 7. The device of claim 4, wherein the atleast one cone sensor includes at least four cone sensors, arranged asat least two pairs of cone sensors, each pair being of substantiallyidentical cone sensors, and each pair representing a different type ofcone sensor, for providing three-dimensional information by at least twomodalities.
 8. The device of claim 1, wherein the first mechanism is asuction source configured for fixing and immobilizing the tissue bysuction.
 9. A tissue characterization probe, comprising: a housing, saidhousing comprising: a structure, formed of a rigid surface of a conicalcross-section, having a diameter in a first direction and an axis in asecond direction; at least one piston sensor; a first force exertingmechanism, associated with the structure, configured to provide a firstforce and to exert said force on a tissue, in the second direction,along the axis, at an acute angle α to the rigid surface, the forcebeing in a direction of narrowing diameter of said conical structure forfixing the tissue to the structure, so as to immobilize the tissue; anda second force exerting mechanism, associated with the structure,configured to press said at least one piston sensor against an externalsurface of the immobilized tissue thereby to provide a counter force andto exert said counter force on the immobilized tissue, wherein saidfirst force exerting mechanism is configured to set at least a componentof the force in opposition to at least a component of the counter force,said structure, said first force exerting mechanism and said secondforce exerting mechanism together being configured to force theimmobilized tissue against the at least one piston sensor, and furtherto force the at least one piston sensor against the immobilized tissue,bringing about an effective contact between the at least one pistonsensor and the immobilized tissue; and a signal communication line, forproviding communication between a signal analyzer and the at least onepiston sensor; and wherein said at least one piston sensor is selectedfrom the group consisting of optical sensor, X-ray sensor, RF sensor, MWsensor, infrared thermography sensor, ultrasound sensor, MR sensor,impedance sensor, a temperature sensor, radioactive-emission sensor,mechanical sensor, and a nonirradiative RF sensor.
 10. Thetissue-characterization probe of claim 9, configured for an applicationselected from the group consisting of extracorporeal application to askin surface, intracorporeal insertion through a body lumen,intracorporeal insertion for a minimally invasive procedure, andapplication to subcutaneous tissue during open surgery.
 11. A system fortissue characterization, comprising: a housing, said housing comprising:a structure, formed of a rigid surface of a conical cross-section,having a diameter in a first direction and an axis in a seconddirection; at least one piston sensor; a first force exerting mechanism,associated with the structure, configured to provide a first force andto exert said force on a tissue, in the second direction, along theaxis, at an acute angle α to the rigid surface, the force being in adirection of narrowing diameter of said conical structure for fixing thetissue to the structure, so as to immobilize the tissue; and a secondforce exerting mechanism, associated with the structure, configured topress said at least one piston sensor against an external surface of theimmobilized tissue thereby to provide a counter force and to exert saidcounter force on the immobilized tissue, wherein said first forceexerting mechanism is configured to set at least a component of theforce in opposition to at least a component of the counter force, saidstructure, said first force exerting mechanism and said second forceexerting mechanism being configured together to force the immobilizedtissue against the at least one piston sensor, and further to force theat least one piston sensor against the immobilized tissue, bringingabout an effective contact between the at least one piston sensor andthe immobilized tissue; a signal analyzer; and a signal communicationline, for providing communication between the signal analyzer and the atleast one piston sensor; and wherein said at east one piston sensor isselected from the group consisting of optical sensor, X-ray sensor, RFsensor, MW sensor, infrared thermography sensor, ultrasound sensor, MRsensor, impedance sensor, a temperature sensor, radioactive-emissionsensor, mechanical sensor, and a nonirradiative RF sensor.
 12. A methodfor tissue characterization, comprising: providing a device for tissuecharacterization, the device comprising: a structure, formed of a rigidsurface of a conical cross-section, having a diameter in a firstdirection and an axis in a second direction; and at least one pistonsensor; applying a force on a tissue, using a first force exertingmechanism, associated with the structure, said force being applied tosaid tissue, in a second direction along the axis, at an acute angle αto the rigid surface, for fixing the tissue to the structure, so as toimmobilize the tissue; and providing a counter force by pressing, usinga second force exerting mechanism, associated with the structure, saidat least one piston sensor against an external surface of theimmobilized tissue and to thereby exert said counter force on theimmobilized tissue, wherein said first force exerting mechanism sets atleast a component of the force in opposition to at least a component ofthe counter force, and said structure, said first force exertingmechanism and said second force exerting mechanism together areconfigured to force the immobilized tissue against the at least onepiston sensor, and further to force the at least one piston sensoragainst the immobilized tissue, bringing about an effective contactbetween the at least one piston sensor and the immobilized tissue;fixing the tissue to the structure, thus immobilizing the tissue; andcharacterizing the tissue with the at least one piston sensor; whereinsaid at least one piston sensor is selected from the group consisting ofoptical sensor, X-ray sensor, RF sensor, MW sensor, infraredthermography sensor, ultrasound sensor, MR sensor, impedance sensor, atemperature sensor, radioactive-emission sensor, mechanical sensor, anda nonirradiative RF sensor.